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Innate Immune System
1. What are the functions of complement?
Opsonisation
Lysis of infected cells
Disposal of immune complexes
(MAC formation)
Activation of mast cells (via anaphylotoxins)
Chemotactic signalling to recruit phagocytes
Also – induction of inflammatory responses
2. Explain the function and mechanism of the classical complement pathway
The classical pathway is activated by immune complexes (antigen-antibody complexes).
It results in the formation of the classical pathway C5 convertase (C4b2a3b) and the
subsequent formation of MAC (C5b6789n), which acts to lyse infected cells. During the
cascade, a number of complement fragments are generated (notably C5a and C3b) which
play crucial roles in the generation of an immune response. C5a is a potent initiator of
inflammation, C3b opsonises cells, encouraging their phagocytosis, and other
complement fragments act to recruit phagocytes.
3. What is the lectin pathway? How does it differ from the classical pathway?
The lectin pathway feeds into the classical pathway, but differs in its activation. Rather
than immune complexes, it is activated by mannose present on the outside of a number of
pathogens (worms, viruses, fungi, some bacteria). Activation of MBL (mannose-binding
lectin) induces the formation of a complex of MASP1 and 2 and MBL which results in
the formation of the classical pathway C5 convertase (C4b2a3b).
4. What is the alternative pathway?
The alternate pathway is a primitive complement pathway activated by endotoxin (lipid
A) and lipopolysaccharide (LPS) present in the bacterial cell wall of gram negative
bacteria (Listeria, a gram positive, also possesses endotoxin – it is the only gram positive
bacteria to do so). Activation of this pathway results in the formation of the alternate
pathway C5 convertase (C3bBb3b) which then feeds into the final lytic pathway of
completment.
5. What are the innate physical defences of the body?
Skin
Mucous membrane defenses:
Tears – lysozymes, phospholipase A
Acid
Cilia
Commensals
Saliva – Histatins
Surfactant proteins A and D
6. What is the final lytic pathway of complement? What purpose does it serve?
C5 is cleaved by either classical or alternate pathway C5 convertase. The C5a fragment
is a potent initiator of inflammation. C5b goes on to complex with other complement
proteins to form the membrane attack complex MAC (C5b6789n) which inserts into the
cell membrane and lyses infected cells.
7. What are phagocytes and what are their functions? What groups of bacteria can
avoid their actions?
Phagocytes include macrophages, neutrophils, NK cells, eosinophils and basophils. They
all ingest foreign pathogens through phagocytosis, a process that is facilitated by
opsonisation. The ingested pathogen is held in a phagosome which fuses with a
lysosome to form a phagolysosome. The pathogen is then subject to a number of
destructive factors including toxic enzymes such as DNAase and acid phosphatase, free
radicals including H202, O2-, OH, acidic pH and Nitric Oxide. Some bacteria are able to
ameliorate the actions of these factors: pneumococci have a thick capsule which prevents
their destruction, staphylococci produce toxins which destroy phagocytes,
Mycobacterium TB is able to survive within macrophages, where it induces chronic
inflammation and the formation of multinucleate giant cells.